The disease caused by Haemophilus influenzae type b is a major cause of bacterial meningitis in children under the age of five years. Protective antibodies to the disease are induced by the capsular polysaccharide of the organism and a vaccine has been developed that utilizes the purified polyribosyl ribitol phosphate (PRP) as the antigen. This vaccine gave 90% protection in adults and in children over 24 months of age, but was ineffective in children under 24 months. Like other polysaccharide vaccines, the PRP does not induce the proliferation of T-helper cells, and re-immunization fails to elicit either booster response or increase in memory cells. A new conjugate vaccine has been developed that uses the PRP linked to diphtheria toxoid (see European Patent No. 0,098,581), which elicits T-cell dependent, booster responses and the production of PRP-specific IgG antibodies. To achieve broader protection in the 2 to 6 month age group and certain high risk groups, the incorporation of certain non-capsular antigens may be required. It has been shown that a monoclonal antibody directed against the outer membrane protein P1 of Haemophilus influenzae b has protective activity in the infant rat model of bacteremia. It has also been demonstrated that rabbit antisera directed against purified P1 also has protective activity in the rat model. The inventors have cloned, sequenced, and expressed in E. coli, the structural gene from P1 from three isolates.
Methods for inducing immunity against disease are constantly improving and there is presently a move towards the use of smaller and better defined materials as antigens. This is being undertaken to minimize or eliminate potential side-effects due to certain native immunogens, while preserving their immunogenicity and ability to confer protection against the disease.